HU201744B - Fungicide comprising imidazole derivative as active ingredient and process for producing the active ingredient - Google Patents

Description

Scope of the description: 7 pages, 1 drawing, Figure 4

EN 201744 β

The present invention relates to a fungicidal composition comprising an imidazole derivative and to the preparation of an active ingredient.

In our European patent application No. 191,514 Al (No. 86,200,092.4) we have described the imidazole-5-carboxylic acid derivatives of formula (IV):

R is optionally substituted phenyl;

R ¹ is optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl;

R ² is optionally substituted alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, aryl or aralkyl; and

X is oxygen or sulfur or -NR'-in which R ³ is hydrogen or alkyl; or

R ² and R ³ , taken together with the adjacent nitrogen atom, may also form a saturated or unsaturated heterocyclic group containing five or six, optionally further one or two heteroatoms.

It has been found that a compound of formula (VI) which is not specifically disclosed in our above-mentioned European Patent Application No. 0 191 514 A1 has a particularly interesting fungicidal effect.

Accordingly, the present invention relates to the active ingredient, to the compound of formula (I) and to the preparation of compound (X).

According to the invention, the compound of formula (I) is prepared by reacting a compound of formula (II): wherein L is a halogen atom or a C 1-4 alkoxy group in the presence of a base, preferably pentanol dissolved in pentanol, with 3-pentanol. .

The leaving group L is a halogen atom, preferably a chlorine or bromine atom, a C 1-4 alkoxy group, preferably a methoxy group.

The process of the invention may be carried out in the presence of an inert solvent, for example, an excess of pentanol may be used as a solvent, but it may be employed without a solvent. It is also possible to use other inert solvents such as dimethoxyethane, dimethylsulfoxide, dimethylformamide or tetrahydrofuran. Most preferably, dimethoxyethane and dimethyl sulfoxide may be used.

Compounds of formula (II) wherein L is halogen are most preferably prepared by reacting a compound of formula (III) with a halogenating agent. The halogenating agent is thionyl chloride, thionyl bromide, phosphorus pentachloride, phosphorus trichloride, and phosphorus tribromide. This reaction may be carried out, if desired, in the presence of an inert solvent such as toluene, benzene, diethyl ether or tetrahydrofuran.

Compounds of formula (II) wherein L is alkoxy may conveniently be prepared by reacting a compound of formula (II) wherein L is halogen with the corresponding sodium alkanoate. This reaction is optionally carried out in an inert solvent such as toluene. or in the presence of an alcohol such as methanol.

The compound of formula (III) is known and can be prepared, for example, by the method of R.G. Jones [J. Am. Chem. Soc., 71, 644 (1949)].

The present invention also relates to a fungicidal composition comprising as active ingredient a compound of formula (I) in admixture with a carrier.

In the composition of the present invention, any substance may be used as a carrier to formulate the active ingredient in a formulation which facilitates application to the site of action: it may be a plant, seed or soil. Also suitable as a carrier is any substance 0 that facilitates the storage, transport or treatment of the composition. The carrier may be a solid or a liquid or a substance which is normally gaseous under pressure but liquefies under pressure. Any carrier which is commonly used to form fungicidal compositions may be used.

Examples of solid carriers include: natural silicas such as 3 diatomaceous earth; magnesium silicates such as talc; magnesium aluminum sulfates, such as attapulgites and vermiculites; aluminum silicates such as kaolinites, montmorillonites and mica; calcium carbonate; > calcium sulfate; synthetic, hydrated silica and synthetic calcium or aluminum silicates; certain elements such as sled and sulfur; natural and synthetic resins such as coumarone resins; poly (vi) nyl chloride and styrene polymers and copolymers; solid poly (chlorophenol; s; bitumen; waxes such as beeswax, paraffin wax and chlorinated mineral waxes; and solid fertilizers such as superphosphates.

»Examples of liquid carriers include: water; alcohols, such as isopropanol and glycols; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic and aryl aliphatic hydrocarbons such as benzene, toluene and xylene; petroleum distillates such as kerosene and light mineral oils; chlorinated hydrocarbons such as carbon tetrachloride, perchlorethylene and trichloroethane. Mixtures of these different liquids are often used.

EN 201744 Β

Fungicidal compositions are often prepared and delivered in a concentrated form which is diluted prior to application. This dilution process is facilitated by the presence of a small amount of a vehicle that is also surfactant. Accordingly, at least one carrier in the composition of the invention is preferably a surfactant. For example, the composition may comprise at least two carriers, at least one of which is a surfactant.

The surfactant may be an emulsifier, a dispersant or a wetting agent; it may also be ionic or nonionic. Examples of surfactants include sodium or calcium salts of polyacrylic acids and lignin sulfonic acids; condensation products of fatty acids having at least 12 carbon atoms or aliphatic amines or acid amides with ethylene oxide and / or propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol; the condensation products of the latter with ethylene oxide and / or propylene oxide; condensation products of fatty alcohols or alkylphenols such as p-octylphenol or p-octylcresol with ethylene oxide and / or propylene oxide; sulphates or sulfonates of the latter condensation products; sulfuric acid or sulfonic acid esters of at least 10 carbon atoms, such as sodium lauryl sulfate, sodium salts of sulphonated castor oil, sodium salts of secondary alkyl sulfuric acid, and sodium salts of alkyl arylsulfonic acids, e.g. benzene; and polymers of ethylene oxide polymers and ethylene oxide-propyl oxide.

For example, the compositions of the present invention may be formulated as wettable powders, dusting agents, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates, and aerosols. The wettable powders contain 25, 50 or 75% by weight of the active ingredient and, in addition to the inert solid carrier, 3-10% by weight of dispersant and, if necessary, 0-10% by weight of stabilizer (s) and / or other excipients such as the drug penetration or adhesion. contain substances. Dusts are generally formulated as dust concentrates, the composition of which is similar to the composition of wettable powders, but does not contain a dispersant, may be diluted in the field by the addition of a further solid carrier, generally resulting in a composition containing from 0.5 to 10% by weight of the active ingredient. The granules are generally made to be 1.676-0.152 mm (corresponding to BS mesh 10 and 100 meshes): these can be produced by agglomeration or impregnation. The particles generally contain from 0.5 to 25% by weight of the active ingredient and from 0 to 10% by weight, for example, a stabilizer, slow release agents and binders. The emulsifiable concentrates generally contain, in addition to the solvent and, if desired, the co-solvent, 1-50% (w / v) active ingredient, 2-20% (w / v) emulsifier and 0-20% w / v other additives such as stabilizer. penetration agents and anticorrosive agents

- contain. Generally, the suspension concentrates are prepared by obtaining a stable, non-sedimenting, easy to flow product; these concentrates generally contain from 10 to 75% by weight of the active ingredient, from 0 to 15% by weight of the dispersant, from 0.1 to 10% by weight of the suspending agent, such as protective colloids and thixotropic agents, from 0 to 10% by weight of other additives such as antifoam, anti-corrosion agent, stabilizer, penetration enhancers and containing adhesives, water or an organic liquid in which the active ingredient is substantially insoluble; in the composition, some organic solids or inorganic salts may be present in dissolved form to prevent sedimentation or, as regards the water content, as antifreeze agents.

The present invention also relates to aqueous dispersions and emulsions, such as compositions, which are obtained by dilution with water from a wettable powder or concentrate of the invention. Said emulsions may be of the water / oil or oil / water type and may have a mayonnaise consistency.

The compositions include other components, such as pesticidal compounds

it may contain, in particular, insecticides, acaricides, herbicides and fungicides.

Particularly noteworthy for the purpose of increasing the potency of the active compounds of the present invention is the use of a carrier which provides release of the fungicidal compound in the environment of the plant to be protected. Such slow release formulations may be injected, for example, around the root of a vineyard; or the compositions may also contain a tackifier component that allows the composition to be applied directly to the stem of the solitary plant.

The present invention is widely applicable to the protection of crops against attack by fungal pathogens. Examples of such crops are grapes and grain crops such as wheat, barley, rice and beans. Normally, the duration of the protective action depends on a number of external factors, such as climatic conditions, which, in addition to the active ingredient, can generally be mitigated by the use of a suitable formulation. Usually, the application is effected by delivering 0.1 to 10 kg of active ingredient per hectare, preferably 0.1 to 1 kg of active ingredient.

EN 201744 Β

The present invention is further illustrated by the following non-limiting examples.

Example 1

Preparation of N- (2,4-dichlorophenyl) -1-n-ethylimidazole-5-carboximic acid (1-ethylpropyl) ester \ t

A mixture of 2.0 g of N- (2,4-dichlorophenyl) -1-methylimidazole-5-carboxylic acid and 50 ml of thionyl chloride is refluxed for 2 hours. The excess thionyl chloride was then evaporated and the residue was suspended in 25 ml of dimethoxyethane, a solution of 0.4 g of sodium in 35 ml of 3-pentanol was added and the mixture was refluxed for 18 hours. After cooling, the solvent was evaporated in vacuo, the residue was taken up in chloroform, washed with water and dried over magnesium sulfate. Chloroform was evaporated in vacuo to give an oily product which was purified by chromatography. The title compound was obtained as a pale yellow oil.

Analyze based on CuHuCl2N5O:

Calculated: C, 56.5; H, 5.6; N, 12.3X;

Received: C 56.5; H, 5.7; N, 12.3X.

Example 2

Preparation of N- (2,4-dichlorophenyl) -1-methylimidazole-5-carboximidic acid (1-ethylpropyl) ester Step a) \ t

Preparation of N- (2,4-Dichloro-phenyl) -1-methyl-thiazole-5-carboximidic acid methyl ester

A solution of thionyl chloride (22.5 mL, 0.3 mol) in toluene (50 mL) was added dropwise over one hour to 54 g (0.2 mol) of N- (2,4-dichlorophenyl) -1-methylimidazol-5-one. Carboxylic acid and 450 ml of toluene are heated under reflux with stirring, and the mixture is refluxed overnight. Toluene (250 ml) was distilled off, and toluene (250 ml) was added to the residue and toluene (300 ml) was distilled off again. To the residue was added sodium methoxide solution in methanol (200 mL, 13.8 g, 0.6 g) at -5 ° C, the resulting mixture was stirred at room temperature overnight and then water (250 mL) was added. the mixture was separated, washed twice with water and dried over anhydrous magnesium sulfate. The organic fraction was evaporated to dryness on a rotary evaporator and the residue was thoroughly treated with hexane. Thus, the product of (a) is obtained in 52.6 g yield.

Step (b):

Preparation of N- (2,4-dichloro-phenyl) -1-methyl-inidazole-5-carboxylic acid (1-ethyl-propyl) ester \ t

To a solution of 993 g (3.5 mol) of the product from step (a) in 3 liters (27.5 mol) of 3-pentanol was added ca. 1.5 g of sodium in small portions until the reaction started. The reaction mixture was then refluxed for 6 hours while the methanol formed during the transesterification was removed until gas-liquid chromatography indicated that the conversion was 99X-OS. An additional 0.5 g of sodium was then added and the mixture was distilled off under a pressure of 100 ml of 3-pentanol at atmospheric pressure. The reaction mixture was then evaporated to dryness on a rotary evaporator, the residue was dissolved in about 3 liters of hexane, washed twice with water and dried over anhydrous magnesium sulfate. The solution was evaporated again on a rotary evaporator to give the title compound of step (b), i.e. Example 2, (1116 g).

Example 3

The fungicidal activity of the compound of formula (I) according to the invention was confirmed by the following tests.

a, The direct protective effect of the compound against the pathogen of the Botrytis cinerea

The study was aimed at direct protection; leaf spray was used. The lower surface of the leaves of the total soluble plants (cv. Cabernet Sauvignon) was sprayed with a solution containing the active ingredient and 0.04 wt. Triton X-155 '(commercial name) polyoxyethylene-octylphenol surfactant 1: 1 vol. ./térf. νίν-acetone in a ratio of 1 to 2; spraying the drug with a tank wagon to obtain 1 kg of active ingredient per hectare; the tanker sprayed 620 liters of solution per hectare. The plants were kept under normal greenhouse conditions for the next 24 hours and the lower surface of the leaves was sprayed with an aqueous solution containing 10 ^s conidium per ml. The infected plants were kept at high humidity for 24 hours, then kept for 5 days under normal greenhouse conditions, and then returned to the high humidity site for an additional 24 hours. The evaluation was performed by comparing the percentage of the treated area with the spores with the control (untreated leaves spore surface).

EN 201744 Β

b) Effect of the compound against the pathogen of the wheat Leptosphaeria nodorum

This study focused on the direct effect on spores; leaf spray was used. The leaf of wheat germs (cv. Mardler) was sprayed by spraying with an aqueous suspension containing 8 x 10 ^s spores per ml in a single leaf condition. The infected plants were kept in a high-humidity compartment for 24 hours prior to treatment, and the plants were sprayed with 1 kg of active substance per hectare using the tanker described under a). After drying, the plants were kept under normal greenhouse conditions for 5 days and evaluated. The evaluation was performed by comparing the percentage of the treated area with the spores with the spore surface of the control (untreated) leaves.

c) Effect of the compound on barley powdery mildew (Erysiphe graminis hordeij pathogen

This study focused on the direct effect on spores; leaf spray was used. The leaves of Golden Promise barley seedlings were infested with powdery mildew conidia one day prior to treatment with the test compound. The infected plants were kept in a greenhouse overnight at ambient temperature and humidity and then sprayed with 1 kg of active substance per hectare using the tank wagon described in a). After drying, the plants were returned to a room where the ambient temperature and humidity were maintained and evaluated for 7 days. The evaluation was performed by comparing the percentage of the treated area with the spores with the spore surface of the control (untreated) leaves.

d) Effect of the compound on the pathogenic agent of Uromyces fabae

This study focused on the direct effect on spores; leaf spray was used. 1 plant per plant was sprayed with an aqueous suspension containing 5 x 10 * spores per ml and a small amount of Triton X-155 surfactant [see Example 3 (a)]; spraying was performed on the top surface of each leaf 20-24 hours prior to treatment with the test compound. The infected plants were then placed in a high moisture compartment overnight, dried under greenhouse conditions at ambient temperature, and the upper surface of the leaves was sprayed with 1 kg of active substance per hectare using the tank wagon described under a). After treatment, the plants were kept at a greenhouse temperature and evaluated 11 to 14 days after treatment. Symptoms were evaluated by comparing the relative density of sporadic spindles observed per plant compared to control plants.

e) In vitro effect of the compound on the pathogens of wheat sprouting (Pseudocercosporella herpotrichoides)

In this study, the in vitro activity of the compound was measured on the fungal pathogen causing wheat sprouting.

The compound to be tested was dissolved or suspended in acetone, and 30 pellets of bulk semisolid potato dextrose agar were added so that the final concentration of the active ingredient was 100 ppm and the acetone was 3.5%. After the agar was applied, the plates were inoculated with mycelia from a 14-day culture of P. herpotrichoides with sets of 6 mm in diameter. Plates were incubated for 12 days at 20 ° C and radial growth from the inoculation site was measured.

The reduction in disease rate in each study was scored by scoring 40 out of the following criteria, compared to the controls sprayed with the diluent.

0: the drug reduces the disease by less than 50%;

1: curbs the disease by about 50-80%;

2: The disease is controlled by more than 80%.

the results of these tests are given in Table I below.

Botrytis

Table I

The degree of fungicide effect

Leptosphaeria Erysiphe Uromyces

2 2

Pseudocercosp

EN 201744 Β

The compound of the invention has a significantly better effect on the compound of the prior art compared to the compound of the prior art. The comparative data shown in Table 1 are shown.

II. table

Comparative data

Test Method:

Pathogen: Erysiphe graminis - Eg (wheat)

Puccinia recondita - Pr (wheat)

P. striiformis - Pet (Wheat)

Type of testing: therapeutic, 3-day infection

Method of application: machine sprayed with large amounts of spray (approx. 1000 liters / ha):% sporulation disease per plant with 5 leaves, followed by%

Results

Compound Dose g / ha Fungicide Activity (Effect X) Sky pr pst Is 196 290 5 33.3 0.0 15.6 Hungarian Patent 10 62.2 10.7 60.9 Example 7 25 87.6 19.5 97.8 compound 50 96.4 74.0 98.8 According to the invention 5 59.7 8.3 70.6 Of formula (I) 10 77.4 - 96.9 compound 25 96.4 66.0 99.6 50 100.0 97.4

Examples of formulations containing the active ingredient

Example 1 45

A solution of 0.015X active ingredient is a compound of formula (I)

6.2 kg of water and acetone in a 1: 1 v / v solution containing 0.02% (v / v) polyoxyethylene sorbitan monolaurate are dissolved.

Example 2

Solution containing 1.3X active substance

Dissolve 4.5 g of the compound of formula (I) in 60 g of 1: 1 v / v water / acetone, containing 0.04% (w / v) polyoxyethylene sorbitan monolaurate, and then make a solution.

Dissolve 1.55 kg in water. 65

Example 3

Powder containing 2X active ingredient g Compound (I) is mixed with 40 g of crude, dry kaolin in a hammer mill. The resulting material was stirred to 100 g of final crude dry kaolin.

Example 4

25 g of xylene, 20 g of cyclohexanone and an emulsifier (calcium dodecylbenzene azulfonate and 10 g of nonylphenyl ethoxylate in 10 g) are added slowly to the emulsifiable concentrate containing 25X of the active ingredient, and then stirred for 10 minutes. and mixing with xylene to a final weight of 100 g.

-611

EN 201744 Β

Example 5

Claims (4)

PATIENT INDIVIDUAL POINTS Concentrate g of surfactant (sodium polymethylmethacrylate) containing 30% active ingredient is dispersed in 500 g of water. 300 g of the compound of formula I are added to the above dispersion and the material is finely ground in a wet mill. Suspending agent (2.25 g of polysaccharide resin) was added and dispersed, followed by an antifreeze (68 g of monoethylene glycol) and a bacterial growth inhibitor (2 g of formaine). The resulting material was added to water to a final weight of 1000 g and then homogenized. A fungicidal composition comprising a biologically active agent, a solid carrier, preferably kaolin, and / or a liquid carrier, preferably a mixture of acetone, xylene, cyclohexanone and / or a surfactant, preferably polyoxyethylene sorbitan monolaurate, calcium dodecylbenzene. sulphate, nonylphenyl ethoxylate and sodium polymethylmethacrylate, polysaccharide resin, and / or antifreeze, preferably monoethylene glycol and / or antibacterial agent, preferably formate, comprising the compound of formula (I) as active ingredient, 0, It contains from 01 to 35 tX. 2. A process for the preparation of the imidazole derivative of the formula (I), wherein the compound of formula (II) wherein L is halogen or C 1-4 alkoxy is reacted with 3-pentanol. 3. The process according to claim 2, wherein the compound of formula (II) is reacted with a solution of sodium 3-pentanolate in 3-pentanol, wherein L is as defined in claim 2. Process according to claim 2 or 3, characterized in that a compound of formula (Π) 30 wherein L is chloro or bromo or methoxy is used. Published by the National Inventory Office, Budapest Responsible for release: Gabriella Gabriella Szvoboda Head of Department R 4974 - KJK 91.3617.66-13-2 Alföldi Printing House Debrecen - Responsible leader: Viktor Szabó CEO -7GB 201744 Β Int Cl ⁵ C 07 D 233/58 C 07 D 233/54 A 01 N 43/50